System and method for safety syringe

ABSTRACT

A system for mixing drug products and injecting includes a syringe body, proximal and distal stopper members disposed in the syringe body, a plunger member, and a needle hub assembly coupled to the distal needle interface of the syringe body. The proximal and distal stopper members form a proximal drug chamber between there between and a distal drug chamber between the distal stopper member and a distal end of the syringe body. The plunger member includes a needle retention feature, an energy-storage member, and an energy-storage member latching member all disposed in disposed in a plunger interior. First and second sizes of the respective proximal and distal drug chambers can be modified by movement of the proximal and distal stopper members relative to the syringe body. The needle is at least partially retractable into plunger interior upon manipulation of the plunger member relative to the syringe body.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application is a continuation of U.S. patent applicationSer. No. 17/121,414, filed on Dec. 14, 2020 under attorney docket numberCM.20012.30.US, and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE,”which is a continuation of U.S. patent application Ser. No. 15/801,259,filed on Nov. 1, 2017 under attorney docket number CM.20012.00, andentitled “SYSTEM AND METHOD FOR SAFETY SYRINGE,” which claims priorityto (1) U.S. Provisional Patent Application Ser. No. 62/416,102, filed onNov. 1, 2016 under attorney docket number CM.30011.00 and entitled“SYSTEM AND METHOD FOR SAFETY SYRINGE”; (2) U.S. Provisional PatentApplication Ser. No. 62/431,382, filed on Dec. 7, 2016 under attorneydocket number CM.30012.00 and entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; (3) U.S. Provisional Patent Application Ser. No. 62/480,276,filed Mar. 31, 2017 under attorney docket number CM.30015.00 and,entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; (4) U.S. ProvisionalPatent Application Ser. No. 62/542,230, filed Aug. 7, 2017 underattorney docket number CM.30013.00 and entitled “CARTRIDGE SAFETYINJECTION SYSTEM AND METHODS.” This application includes subject mattersimilar to the subject matter described in the following co-owned U.S.patent applications: (1) U.S. Utility patent application Ser. No.14/696,342, filed Apr. 24, 2015, entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; (2) U.S. Utility patent application Ser. No. 14/543,787, filedNov. 17, 2014, entitled “SYSTEM AND METHOD FOR DRUG DELIVERY WITH ASAFETY SYRINGE”; (3) U.S. Utility patent application Ser. No.14/321,706, filed Jul. 1, 2014, entitled “SAFETY SYRINGE”; (4) U.S.Utility patent application filed on Nov. 1, 2017 under attorney docketnumber CM.20011.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”;(5) U.S. Utility patent application filed on Nov. 1, 2017 under attorneydocket number CM.20015.00 and, entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; and (6) U.S. Utility patent application filed on Nov. 1, 2017under attorney docket number CM.20013.00 and, entitled “CARTRIDGE SAFETYINJECTION SYSTEM AND METHODS.” The contents of the aforementioned patentapplications are hereby expressly and fully incorporated by reference intheir entirety, as though set forth in full.

FIELD OF THE INVENTION

The present invention relates generally to injection systems, devices,and processes for facilitating various levels of control over fluidinfusion, and more particularly to systems and methods related tomultiple chamber safety syringes in healthcare environments.

BACKGROUND

Millions of syringes, such as that depicted in FIG. 1A (2), are consumedin healthcare environments every day. A typical syringe (2) comprises atubular body (4), a plunger (6), and an injection needle (8). As shownin FIG. 1B, such a syringe (2) may be utilized not only to inject fluidinto a patient, but also to withdraw or expel fluid out of or into acontainer such as a medicine bottle, vial, bag, or other drugcontainment system (10). Indeed, due to regulatory constraints in somecountries such as the United States as well as sterility maintenanceconcerns, upon use of a medicine bottle (10) with a syringe (2) as shownin a particular patient's environment, such medicine bottle may only beutilized with a single patient and then must be disposed of—causingsignificant medical waste from bottle and remaining medicine disposal,and even contributing to periodic shortages of certain critical drugs.Referring to FIG. 2A, three Luer-type syringes (12) are depicted, eachhaving a Luer fitting geometry (14) disposed distally, so that they maybe coupled with other devices having similar mating geometry, such asthe Luer manifold assembly (16) depicted in FIG. 2B. The Luer manifoldassembly of FIG. 2B may be used to administer liquid drugs to thepatient intravenously with or without the use of an intravenous infusionbag. The Luer fittings (14) of the syringes of FIG. 2A may be termed the“male” Luer fittings, while those of FIG. 2B (18) may be termed the“female” Luer fittings; one of the Luer interfaces may be threaded (inwhich case the configuration may be referred to as a “Luer lock”configuration) so that the two sides may be coupled by relativerotation, which may be combined with compressive loading. In otherwords, in one Luer lock embodiment, rotation, possibly along withcompression, may be utilized to engage threads within the male fitting(14) which are configured to engage a flange on the female fitting (18)and bring the devices together into a fluid-sealed coupling. In anotherembodiment, tapered interfacing geometries may be utilized to providefor a Luer engagement using compression without threads or rotation(such a configuration may be referred to as a “slip-on” or “conical”Luer configuration). While such Luer couplings are perceived to berelatively safe for operators, there is risk of medicinespilling/leaking and parts breakage during assembly of a Luer coupling.The use of needle injection configurations, on the other hand, carrieswith it the risk of a sharp needle contacting or stabbing a person orstructure that is not desired. For this reason, so called “safetysyringes” have been developed.

One embodiment of a safety syringe (20) is shown in FIG. 3 , wherein atubular shield member (22) is spring biased to cover the needle (8) whenreleased from a locked position relative to the syringe body (4).Another embodiment of a safety syringe (24) is shown in FIGS. 4A-4B.With such a configuration, after full insertion of the plunger (6)relative to the syringe body (4), the retractable needle (26) isconfigured to retract (28, 26) back to a safe position within thetubular body (4), as shown in FIG. 4B. Such a configuration which isconfigured to collapse upon itself may be associated with bloodspatter/aerosolization problems, the safe storage of pre-loaded energywhich may possible malfunction and activate before desirable, loss ofaccuracy in giving full-dose injections due to residual dead spacewithin the spring compression volume, and/or loss of retraction velocitycontrol which may be associated with pain and patient anxiety.

Further complicating the syringe marketplace is an increasing demand forpre-filled syringe assemblies such as those depicted in FIGS. 5A and 5B,which generally comprise a syringe body, or “drug enclosure containmentdelivery system”, (34), a plunger tip, plug, or stopper (36), and adistal seal or cap (35) which may be fitted over a Luer type interface(FIG. 5A shows the cap 35 in place; FIG. 5B has the cap removed toillustrate the Luer interface 14). Liquid medicine may reside in thevolume, or medicine reservoir, (40) between the distal seal and thedistal end (37) of the plunger tip (36). The plunger tip (36) maycomprise a standard butyl rubber material and may be coated, such aswith a biocompatible lubricious coating (e.g., polytetrafluoroethylene(“PTFE”)), to facilitate preferred sealing and relative motioncharacteristics against the associated syringe body structure andmaterial. The proximal end of the syringe body (34) in FIG. 5B comprisesa conventional integral syringe flange (38), which is formed integral tothe material of the syringe body (34). The flange (38) is configured toextend radially from the syringe body (34) and may be configured to be afull circumference, or a partial circumference around the syringe body(34). A partial flange is known as a “clipped flange” while the other isknown as a “full flange.” The flange is used to grasp the syringe withthe fingers to provide support for pushing on the plunger to give theinjection. The syringe body (34) preferably comprises a translucentmaterial such as a glass or polymer. To form a contained volume withinthe medicine chamber or reservoir (40), and to assist with expulsion ofthe associated fluid through the needle, a plunger tip (36) may bepositioned within the syringe body (34). The syringe body (34) maydefine a substantially cylindrical shape (i.e., so that a plunger tip 36having a circular cross sectional shape may establish a seal against thesyringe body (34)), or be configured to have other cross sectionalshapes, such as an ellipse.

Such assemblies are desirable because they may be standardized andproduced with precision in volume by the few manufacturers in the worldwho can afford to meet all of the continually changing regulations ofthe world for filling, packaging, and medicine/drug interfacingmaterials selection and component use. Such simple configurations,however, generally will not meet the new world standards for single-use,safety, auto-disabling, and anti-needle-stick. Thus certain suppliershave moved to more “vertical” solutions, such as that (41) featured inFIG. 5C, which attempts to meet all of the standards, or at least aportion thereof, with one solution; as a result of trying to meet thesestandards for many different scenarios, such products may havesignificant limitations (including some of those described above inreference to FIGS. 3-4B) and relatively high inventory and utilizationexpenses.

Moreover, an increasing number of injectable liquids (e.g., medicines)have an additional requirement that two or more components must becombined to form an injectable combination or solution shortly beforedelivery into a patient. While the multiple components can be mixed in aseparate open container before the injectable combination is taken upinto a syringe, such mixing in an open container and drawing into asyringe can be inaccurate and lead to loss of components or theinjectable combination. Further, drawing the injectable combination intoa syringe can lead to unnecessary exposure of a user to an uncappedneedle.

In addition, an increasing number of injectable liquids (e.g.,medicines) have yet another requirement that time of exposure of theinjectable liquid to metals (e.g., stainless steel of a needle) beminimized.

There is a need for injection systems which address the shortcomings ofcurrently-available configurations. In particular, there is a need formultiple chamber safety injection solutions which may utilize theexisting and relatively well-controlled supply chain of conventionallydelivered pre-filled syringe assemblies such as those described inreference to FIGS. 5A and 5B.

SUMMARY

Embodiments are directed to injection systems. In particular, theembodiments are directed to multiple chamber safe injection systems thatmove the needle into a protected configuration to minimize accidentaluser injury and contamination with used needles.

In one embodiment, a system for mixing drug products and injectingincludes a syringe body defining a proximal opening and a distal needleinterface at a distal end thereof. The system also includes proximal anddistal stopper members disposed in the syringe body, forming a proximaldrug chamber between the proximal and distal stopper members and adistal drug chamber between the distal stopper member and the distal endof the syringe body. The system further includes a plunger memberdefining a plunger interior and configured to be manually manipulated toinsert the proximal stopper member relative to the syringe body. Theplunger member includes a needle retention feature disposed in theplunger interior, an energy-storage member disposed in the plungerinterior, and an energy-storage member latching member disposed in theplunger interior. The system further includes a needle hub assemblycoupled to the distal needle interface of the syringe body. The needlehub assembly includes a needle having a needle proximal end feature, ahub, and a needle latching member configured to couple the needle to thehub. First and second sizes of the respective proximal and distal drugchambers can be modified by movement of the proximal and distal stoppermembers relative to the syringe body. The needle is at least partiallyretractable into plunger interior upon manipulation of the plungermember relative to the syringe body to transform the energy-storagemember latching member from a latched state to an unlatched state.

In another embodiment, a system for mixing drug products and injectingincludes a cartridge body defining a proximal opening and a distalneedle interface at a distal end thereof. The system also includesproximal and distal stopper members disposed in the cartridge body,forming a proximal drug chamber between the proximal and distal stoppermembers and a distal drug chamber between the distal stopper member andthe distal end of the cartridge body. The system further includes aplunger member defining a plunger interior and configured to be manuallymanipulated to insert the proximal stopper member relative to thecartridge body. The plunger member includes a needle retention featuredisposed in the plunger interior, an energy-storage member disposed inthe plunger interior, and an energy-storage member latching memberdisposed in the plunger interior. The system further includes a needlehub assembly coupled to the distal needle interface of the cartridgebody. The needle hub assembly includes a needle having a needle proximalend feature, a hub, and a needle latching member configured to couplethe needle to the hub. First and second sizes of the respective proximaland distal drug chambers can be modified by movement of the proximal anddistal stopper members relative to the cartridge body. The needle is atleast partially retractable into plunger interior upon manipulation ofthe plunger member relative to the cartridge body to transform theenergy-storage member latching member from a latched state to anunlatched state.

In one or more embodiments, the needle is configured to pierce entirelythrough at least the distal stopper member to be retracted into theplunger interior. The energy-storage member latching member may beintercoupled between an interior surface of the plunger member and theneedle retention feature. The proximal and distal drug chambers mayrespectively contain first and second components of a drug to be mixedtogether prior to injecting into a patient.

In one or more embodiments, the system has a transport configurationwherein the needle proximal end feature is disposed in the distal drugchamber, a transfer configuration wherein the needle proximal endfeature has at least partially pierced the distal stopper member and isat least partially disposed in the proximal drug chamber, and a mixedconfiguration wherein the proximal and distal stopper members are incontact with each other, thereby transferring a first drug componentfrom the proximal drug chamber to the distal drug chamber to mix thefirst drug component with a second drug component in the distal drugchamber. The needle may include a distal end opening, a middle openingdisposed in the distal drug chamber when the system is in the transport,transfer, and mixed configurations, and a proximal opening disposed inthe proximal drug chamber when the system is in the transport andtransfer configurations.

In one or more embodiments, the needle also includes a plurality ofproximal openings, the proximal opening being one of the plurality ofproximal openings. At least some of the proximal openings may bedisposed in the proximal drug chamber when the system is in thetransport and transfer configurations, and at least some of the proximalopenings may be occluded by the proximal stopper member when the systemis in the mixed configuration. The proximal stopper member may include aplug configured to occlude at least some of the proximal openings whenthe system is in the mixed configuration. A length of the plug may begreater than a distance between a proximal most opening of the pluralityof proximal openings and a distal most opening of the plurality ofproximal openings.

In one or more embodiments, the syringe or cartridge body includes aposition indicator configured to be adjacent with a distal end of thedistal stopper when the when the system is in the mixed configuration.The plunger member may include a retention clip configured to beselectively coupled to the syringe or cartridge body when the system isin the mixed configuration to prevent proximal movement of the plungermember relative to the syringe or cartridge body. The retention clip maybe configured to generate an audible signal when the retention clip isselectively coupled to the syringe or cartridge body.

In one or more embodiments, the proximal and distal stoppers includerespective first and second polymer coatings on respective distal andproximal surfaces thereof, such that the proximal drug chamber isdefined by the syringe or cartridge body and the first and secondpolymer coatings. The distal stopper may have a funnel that tapers in aproximal direction, and a space disposed at a tapered proximal end ofthe funnel.

In one or more embodiments, the hub includes a collet and a sleeve. Thecollet may be configured to removably couple the needle hub assembly tothe distal needle interface of the cartridge body when the sleeve isdisposed around the collet. The hub may include a sealing memberconfigured to surround and form a fluid tight seal around an externalsurface of the needle.

In one or more embodiments, the system also includes a transfer pipedisposed in the distal drug chamber. The needle and the transfer pipemay be removably coupled when the needle hub assembly is removablycoupled to the distal needle interface of the cartridge body. Thetransfer pipe may have a reduced diameter section at a distal endthereof configured to secure the needle thereto.

In still another embodiment, a system for injecting includes a syringebody defining a proximal opening and a distal needle interface at adistal end thereof. The system also includes proximal and distal stoppermembers disposed in the syringe body, forming a drug chamber between theproximal and distal stopper members. The system further includes aplunger member defining a plunger interior and configured to be manuallymanipulated to insert the proximal stopper member relative to thesyringe body. The plunger member includes a needle retention featuredisposed in the plunger interior, an energy-storage member disposed inthe plunger interior, and an energy-storage member latching memberdisposed in the plunger interior. The system further includes a needlehub assembly coupled to the distal needle interface of the syringe body.The needle hub assembly includes a needle having a needle proximal endfeature, a hub, and a needle latching member configured to couple theneedle to the hub. The needle proximal end feature is configured topenetrate the distal stopper member into the drug chamber when thesystem is in an injection configuration. The needle is at leastpartially retractable into plunger interior upon manipulation of theplunger member relative to the syringe body to transform theenergy-storage member latching member from a latched state to anunlatched state.

In one or more embodiments, the drug chamber contains a drug that issensitive to degradation during storage by contact with the metalmaterial of the needle. The proximal and distal stoppers may includerespective first and second polymer coatings on respective distal andproximal surfaces thereof, such that the drug chamber is defined by thesyringe body and the first and second polymer coatings.

In one or more embodiments, the system has a transport configurationwherein the needle proximal end feature is not disposed inside the drugchamber. The needle proximal end feature may have pierced through thedistal stopper and is disposed in the drug chamber, thereby providing adrug exit pathway to inject the drug into the patient when the system isin the injection configuration.

In one or more embodiments, the needle includes a distal end opening, amiddle opening disposed in the drug chamber when the system is in thetransport and injection configurations, and a proximal opening disposedin the drug chamber when the system is in the injection configuration.

In yet another embodiment, a method for mixing and injecting medicineinto a patient includes providing a system. The system includes asyringe body defining a proximal opening and a distal needle interfaceat a distal end thereof. The system also includes proximal and distalstopper members disposed in the syringe body, forming a proximalmedicine chamber between the proximal and distal stopper members and adistal medicine chamber between the distal stopper member and the distalend of the syringe body. The system further includes a plunger memberdefining a plunger interior and configured to be manually manipulated toinsert the proximal stopper member relative to the syringe body.Moreover, the system includes a needle member having a distal needletip, a medicine passage, a plurality of transfer openings, and aproximal end. The method also includes advancing the plunger member topierce the proximal end of the needle member through the distal stopperto allow the passage of a first medicine component from the proximalmedicine chamber through the medicine passage, and into the distalmedicine chamber to allow mixing of the first medicine component with asecond medicine component in the distal medicine chamber to form a mixedmedicine.

In another embodiment, a method for mixing and injecting medicine into apatient includes providing a system. The system includes a cartridgebody defining a proximal opening and a distal needle interface at adistal end thereof. The system also includes proximal and distal stoppermembers disposed in the cartridge body, forming a proximal medicinechamber between the proximal and distal stopper members and a distalmedicine chamber between the distal stopper member and the distal end ofthe cartridge body. The system further includes a plunger memberdefining a plunger interior and configured to be manually manipulated toinsert the proximal stopper member relative to the cartridge body.Moreover, the system includes a needle member having a distal needletip, a medicine passage, a plurality of transfer openings, and aproximal end. The method also includes advancing the plunger member topierce the proximal end of the needle member through the distal stopperto allow the passage of a first medicine component from the proximalmedicine chamber through the medicine passage, and into the distalmedicine chamber to allow mixing of the first medicine component with asecond medicine component in the distal medicine chamber to form a mixedmedicine.

In one or more embodiments, the method also includes advancing theplunger member to inject the mixed medicine into a patient. The methodmay include automatically retracting the distal needle tip into thesyringe body when the mixed medicine has been injected into the patient.

In still another embodiment, a method for injecting medicine into apatient includes providing a system. The system includes a syringe bodydefining a proximal opening and a distal needle interface at a distalend thereof. The system also includes proximal and distal stoppermembers disposed in the syringe body, forming a medicine chamber betweenthe proximal and distal stopper members and a distal medicine chamberbetween the distal stopper member and the distal end of the syringebody. The system further includes a plunger member defining a plungerinterior and configured to be manually manipulated to insert theproximal stopper member relative to the syringe body. Moreover, thesystem includes a needle member having a distal needle tip, a medicinepassage, a plurality of transfer openings, and a proximal end. Themethod also includes advancing the plunger member to pierce the proximalend of the needle member through the distal stopper to allow the passageof a medicine from the proximal medicine chamber through the medicinepassage, and into the distal medicine chamber.

In one or more embodiments, the method also includes advancing theplunger member to inject the medicine into a patient. The method mayinclude automatically retracting the distal needle tip into the syringebody when the mixed medicine has been injected into the patient.

In yet another embodiment, a system for mixing drug products andinjecting includes a syringe body defining a proximal opening and adistal needle interface at a distal end thereof. The system alsoincludes proximal and distal stopper members disposed in the syringebody, forming a proximal drug chamber between the proximal and distalstopper members and a distal drug chamber between the distal stoppermember and the distal end of the syringe body. The system furtherincludes a plunger member defining a plunger interior and configured tobe manually manipulated to insert the proximal stopper member relativeto the syringe body. The plunger member includes a needle retentionfeature disposed in the plunger interior, an energy-storage memberdisposed in the plunger interior, and an energy-storage member latchingmember disposed in the plunger interior. Moreover, the system includes aneedle hub assembly coupled to the distal needle interface of thesyringe body. The needle assembly includes a needle having a needleproximal end feature, a hub, and a needle latching member configured tocouple the needle to the hub. First and second sizes of the respectiveproximal and distal drug chambers can be modified by movement of theproximal and distal stopper members relative to the syringe body. Theneedle is at least partially retractable into plunger interior uponmanipulation of the plunger member relative to the syringe body totransform the energy-storage member latching member from a latched stateto an unlatched state. The distal drug chamber contains a partialvacuum.

In one or more embodiments, the distal stopper member includes aproximal gate having a closed configuration where the needle proximalend feature cannot pass through the proximal gate, and an openconfiguration where the needle proximal end feature can pass through theproximal gate. The proximal gate may include a pair of movable armsoperatively coupled to a pair of spring elements. The pair of springelements may bias the proximal gate in the closed configuration. Theneedle proximal end feature may include a proximal shoulder that cannotpast through the proximal gate in the closed configuration, but can passthrough the proximal gate in the open configuration. The needle mayinclude a distal shoulder that cannot past through the proximal gate inthe closed configuration, but can pass through the proximal gate in theopen configuration, and where the distal shoulder is distal of theproximal shoulder. The proximal gate may include a pair of movable armsoperatively coupled to a pair of self-energizing hinges.

In another embodiment, a method for mixing and injecting medicine into apatient includes providing a system. The system includes a syringe bodydefining a proximal opening and a distal needle interface at a distalend thereof. The system also includes proximal and distal stoppermembers disposed in the syringe body, forming a proximal medicinechamber between the proximal and distal stopper members and a distalmedicine chamber between the distal stopper member and the distal end ofthe syringe body. The system further includes a plunger member defininga plunger interior and configured to be manually manipulated to insertthe proximal stopper member relative to the syringe body. Moreover, thesystem includes a needle member having a distal needle tip, a medicinepassage, a plurality of transfer openings, and a proximal end. Thedistal medicine chamber contains a partial vacuum. The method alsoincludes advancing the plunger member to pierce the proximal of theneedle member through the distal stopper member to allow the partialvacuum in the distal drug chamber to draw a first medicine componentfrom the proximal medicine chamber through the medicine passage, andinto the distal medicine chamber to allow mixing of the first medicinecomponent with a second medicine component in the distal medicinechamber to form a mixed medicine.

In one or more embodiments, the method also includes moving the distalstopper member distally to collapse a space in the distal medicinechamber such that an injection can be given with the system withoutpurging the system. The method may also include advancing the plungermember to inject the medicine into a patient. The method may furtherinclude automatically retracting the distal needle tip into the syringebody when the medicine has been injected into the patient.

The aforementioned and other embodiments of the invention are describedin the Detailed Description which follows.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects of embodiments are described in furtherdetail with reference to the accompanying drawings, in which the sameelements in different figures are referred to by common referencenumerals, wherein:

FIGS. 1A-5C illustrate various aspects of conventional injection syringeconfigurations.

FIGS. 6A-7P illustrate various aspects of syringe based dual chambersafe injection systems wherein a distal needle end/tip may be withdrawninto a protected configuration after use according to variousembodiments.

FIGS. 8A and 8B illustrate harpoon coupling interfaces according to twoembodiments that can be used with dual chamber safe injection systemsaccording to various embodiments.

FIGS. 9A and 9B illustrate various aspects of a mixed configurationlatch according to one embodiment that can be used with dual chambersafe injection systems according to various embodiments.

FIGS. 10A and 10B illustrate various aspects of a mixed configurationindicator according to one embodiment that can be used with dual chambersafe injection systems according to various embodiments.

FIGS. 11A-11E illustrate various aspects of the dual chamber safeinjection systems depicted in FIGS. 6A-10B in increasing detail todemonstrate various aspects of the systems.

FIGS. 12A-12D illustrate various aspects of a distal stopper bushingaccording to one embodiment that can be used with dual chamber safeinjection systems according to various embodiments.

FIGS. 12E-12F illustrate various aspects of a guide disc according toone embodiment that can be used with dual chamber safe injection systemsaccording to various embodiments.

FIGS. 13A-13C illustrate various aspects of a proximal stopper screwaccording to one embodiment that can be used with dual chamber safeinjection systems according to various embodiments.

FIGS. 14A-16H illustrate various aspects of cartridge based dual chambersafe injection systems wherein a distal needle end/tip may be withdrawninto a protected configuration after use according to variousembodiments.

FIGS. 17A-18G illustrate various aspects of dual chamber safe injectionsystems configured to have a user attachable needle which utilizes aLuer type coupling according to various embodiments.

FIGS. 19A-19D illustrate a dual chamber medicine mixing and deliverysystem for delivering a medicine to a patient via an IV port or otherdelivery method not involving an injection into the patient.

FIGS. 20A-20D illustrate a safe injection system according to oneembodiment for storage and delivery of a drug which is sensitive tocontact with stainless steel.

FIGS. 21A-21D illustrate a needle latching mechanism with adjustableforce to unlatch the needle

FIGS. 22A-22D illustrate an embodiment of the internal mechanism of asafe injection system for storage and delivery of a drug which issensitive to contact with stainless steel.

FIGS. 23-34 illustrate various aspects of vacuum assisted dual chambersafe injection systems wherein a distal needle end/tip may be withdrawninto a protected configuration after use according to variousembodiments, including exemplary distal stopper bushings for usetherein, which are shown in FIGS. 25, 26, and 34 .

In order to better appreciate how to obtain the above-recited and otheradvantages and objects of various embodiments, a more detaileddescription of embodiments is provided with reference to theaccompanying drawings. It should be noted that the drawings are notdrawn to scale and that elements of similar structures or functions arerepresented by like reference numerals throughout. It will be understoodthat these drawings depict only certain illustrated embodiments and arenot therefore to be considered limiting of scope of embodiments.

DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS Exemplary Dual ChamberSafe Syringe Systems

Referring to FIGS. 6A-6B, a perspective and a longitudinal cross sectionview of a dual chamber safe injection system are shown, with aconventional off-the-shelf pre-filled syringe body (34) withconventional proximal and distal stopper members (32, 36) disposedtherein. The proximal and distal stopper members (32, 36) together withthe syringe body (34) define proximal and distal medicine chambers (40,42). The proximal and distal stopper members (36, 37) occlude theproximal and distal ends of the proximal medicine chamber (40). Thedistal stopper member (36) occludes a proximal end of the distalmedicine chamber (42). A needle coupling assembly (606) is disposed atthe distal end of the distal medicine chamber (42) with a needle covermember (63) installed for storage. The dual chamber safe injectionsystem controls transfer of a first medicine component from the proximalmedicine chamber (40) to the distal medicine chamber (42) and exit of amixed/combined medicine from the distal medicine chamber (42) distallysubject to sequential insertion of a plunger assembly relative to thesyringe body (34) to various degrees by a user. The plunger assemblyincludes the proximal stopper member (32), a plunger housing member (69)and a plunger manipulation interface (128). The first medicine componentlocated in the proximal medicine chamber (40) may be a liquid such asaqueous or oil based medicine solutions, a gel, or the first medicinecomponent may be a diluent for mixing with the second medicine componentin the distal medicine chamber (42). The second medicine component inthe distal medicine chamber (42) may be a dry form medicine such as apowder, microspheres, emulsion, lyophilized or freeze dried medicine, ora cake like solid medicine. The second medicine component in the distalmedicine chamber (42) may also be a liquid that mixes with the firstmedicine component from the proximal medicine chamber (40).

The dual chamber safe injection system has a staked needle configurationwherein upon presentation to the user, a needle assembly, comprising aneedle coupling assembly (606), a needle distal end/tip (48), a needlejoining member (83—see, for example, FIG. 6E), and a needle proximal end(50) are mounted in position ready for injection after removal of aneedle cover member (63) which may comprise an elastomeric sealingmaterial on its internal surface to interface with the needle distal end(48) or the distal housing portion (610) during storage. Alternatively,the needle cover member (63) may comprise a vent (not shown) forallowing pressure resulting from the transfer and mixing of the medicinecomponents to escape from inside the syringe body (34) while preventingcontamination from entering the syringe body (34). While, the stakedneedle is depicted as mounted in position, the staked needle may beremovably coupled to the syringe body (34) using a Luer interface (notshown), with the proximal end (50) of the needle member extendingthrough the Luer interface and into the distal medicine chamber (42). Inthe embodiments depicted in FIGS. 6A-22D, a significant portion of thesafe needle retraction hardware resides within a plunger housing.

Referring to FIGS. 6C and 6D, at initial assembly time (i.e., in thefactory or processing facility—not in the field in a “staked needle”configuration), the proximal housing assembly (608) is configured tosnap-fit (i.e., using a snap ring element 604 comprising or coupled tothe proximal housing assembly) over a slightly recessed radial portion(602) of the syringe body which is formed into the syringe body uponmanufacture of the syringe body.

Referring to FIGS. 6E and 6F, the needle spine assembly (76) includes aninjection member having a distal needle end (48), and a needle proximalend (50) coupled to a needle joining member (83). The needle joiningmember (83) is configured to have a necked-down or radially-reducedportion (111) that is configured to interface with a latching member(612) and movable block member (614) such that during injection, theneedle distal end (48), needle joining member (83), and needle proximalend (50) remain fixed in position relative to the syringe body (34)during injection, but after complete insertion of the plunger assemblyrelative to a small diameter flange (33—see, for example, FIG. 7N)(i.e., near or after full expulsion of the medicine which may becontained within the distal medicine chamber 42 of the syringe body 34),the movable block member (614) is advanced relative to the distalhousing portion (610) such that the plurality (two are illustrated) ofcantilevered latch members (616) of the latch member (612) are urged outof the way by the movable block member (614). In particular, the needlespine assembly (76) is forced distally by complete advancement of theplunger assembly, advancing the movable block member (614) to move thecantilevered latch members (616). Moving the cantilevered latch members(616) allows the needle distal end (48), joining member (83), andproximal end (50) to be retracted through their coupling, therebyplacing the needle distal end (48) safely within the plunger housingmember (69). Alternatively, the needle distal end (48) may be retractedto a position below the outer surface of the distal housing portion(610) to safely protect the sharp point from the user. In other words,the cantilevered latch members (616) retain the position of the needledistal end (48) during injection and needle/syringe assembly, until theyare pushed out of the way by the movable block member (614) at fullplunger insertion, after which the needle is free to be automaticallywithdrawn when triggered by further distal movement of the needle spineassembly (76) as described in U.S. patent application Ser. Nos.14/696,342 and 62/416,102, which were previously incorporated byreference herein.

In one embodiment, the plunger assembly includes a coupling member thatcreates a gap in the plunger assembly, which allows the plungermanipulation interface to continue to move distally after the distalstopper member has reached the distal end of the syringe body to ejectsubstantially all of the mixed medicine from the syringe body. In thisembodiment, the plunger manipulation interface is pushed distally asmall distance after full injection to collapse the coupling member andthe gap, release the cantilevered latch members, couple the needle spineassembly to an energy storage member, and release the energy storagemember to retract the coupled needle spine assembly at least into thesyringe body. This embodiment is described in further detail in U.S.patent application Ser. No. 62/416,102, which was previouslyincorporated by reference herein.

FIG. 6E illustrates aspects of a needle spine assembly (76), comprisingthe elements of a needle assembly without the needle coupling assembly(606). The distal portion (48) of the needle spine assembly (76)comprises a sharpened hypodermic needle tip formed on an injectionmember (78). As shown in FIGS. 6G and 6H, the needle proximal end (50)also comprises a sharped tip (86) that is formed into a coupling memberthat forms the distal portion. A generally hollow joining member (83)couples the coupling member to the tubular injection member (78). Theinjection member (78), sharpened tip (86) on the needle proximal end(50), and hollow joining member (83) may be held together withinterference fits, welds, and/or adhesives. The most proximal end (84)of the needle proximal end (50) in the depicted embodiment comprises a“harpoon” style geometry configured to stab into and hold onto acompliant member to which it may be interfaced, as described in furtherdetail below, for withdrawal of the needle spine assembly (76) into theplunger housing member (69). The needle proximal end (50) may be formedfrom a thin sheet metal component using laser cutting, etching,stamping, and/or machining techniques, for example. Other aspects of theneedle spine assembly (76), such as flow paths therethrough and flowblockages, are depicted in at least FIGS. 6M-60 and described below.

FIG. 6P illustrates a detailed cross sectional view of a needle couplingassembly (606) snapped onto a syringe body (34). FIGS. 6I-6L illustratepartial perspective wireframe views to more directly visualize thelatching member (612) and cantilevered latch members (616) relative tothe needle portions (48, 83, 50, 111). The function of the latchingmember (612) and cantilevered latch members (616) in needle retractionare described in U.S. patent application Ser. Nos. 14/696,342 and62/416,102, which were previously incorporated by reference herein.

FIG. 6P also illustrates a distal seal (620) configured to provide aseal between the distal medicine chamber (42) in a medicine container(e.g., syringe body (34)) and the exterior surfaces of the needle spineassembly (76). Preferably, the distal seal (620) is configured toprovide a seal around the outside of the needle joining member (83).This seal is further configured to provide a seal between the distalmedicine chamber (42) and the interior surfaces of the needle couplingassembly (606). FIG. 6P also shows a snap fit (630) between a distal endof the medicine container (e.g., syringe body (34)) and a proximal endof the needle coupling assembly (606).

Returning to FIGS. 6A-6B, for example, a dual chamber safe injectionsystem comprises a conventional syringe body (34), fitted with proximaland distal plunger tips (32, 36) configured to be pierced by proximalneedle end (50) at an appropriate time to assist with medicationtransfer and needle retraction; the proximal plunger tip (32) is coupledto a plunger manipulation interface (128) by a plunger housing member(69) defining an inner volume occupied by various other portions of theassembly, as described below, which are configured to retract the needleat an appropriate time in the sequence of use. A needle couplingassembly (606) described above is included in the illustratedembodiment; other embodiments may comprise Luer type needle assemblycoupling to the syringe body (34). The depicted version of the syringebody (34) comprises a small diameter flange (33) coupled to theconventional integral syringe flange (38), which has a geometry that maybe manipulated or interfaced between the index and middle fingers of theoperator, for example, while a thumb of the operator is interfaced withthe plunger manipulation interface (128). FIGS. 6A and 6B illustratepre-utilization assemblies with a needle cover (63) in place tomechanically isolate the distal needle end (48). The needle cover (63)may be removed and the assembly readied for injection into a patient.

As shown in FIG. 6M, the proximal and distal stopper members (32, 36),together with the syringe body (34) define a proximal medicine chamber(40) with the dual chamber safe injection system in a transportconfiguration. In particular, because the distal end of the proximalstopper member (32) and the proximal end of the distal stopper member(36) are each coated with a lubricious polymer coating (e.g., PTFE), thefirst and second polymer coatings of the proximal and distal stoppermembers (32, 36), together with the syringe body (34) define theproximal medicine chamber (40). The lubricious polymer coating alsoserves to isolate the rubber of the proximal and distal stopper members(32, 36) from the medicine and medicine components. The proximal anddistal stopper members (32, 36) may be oriented as shown in FIG. 6M orthe distal stopper may be flipped so the lubricious coating faces thedistal medicine chamber (42) such that the second drug component in thedistal medicine chamber (42) contacts the lubricious coating forstorage. In the case of the flipped stopper, the needle guide assemblymay be held in place by a centering guide disc shown in FIG. 12F anddescribed below. In an alternative embodiment, the proximal and distalstopper members (32, 36) are rubber without a lubricious polymercoating.

Because the proximal stopper member (32) is coupled to the plungerhousing member (69) and the plunger manipulation interface (128),distally directed force applied to the plunger manipulation interface(128) will move the proximal stopper member (32) in a distal directionrelative to the syringe body (34). Because the proximal medicine chamber(40) is prefilled with a substantially incompressible liquid and becausein the transport configuration depicted in FIG. 6M there is no path forthe incompressible liquid to escape the proximal medicine chamber (40),distal movement of the proximal stopper member (32) results in distalmovement of the distal stopper member (36).

As shown in FIG. 6N, after the distal stopper member (36) has been moveddistally relative to the syringe body (34) to place the dual chambersafe injection system into a transfer configuration, the needle proximalend (50) has pierced the distal stopper member (36) and partiallyentered the proximal medicine chamber (40). Indeed transferconfiguration depicted in FIG. 6N, a transfer pipe (46) portion of theneedle proximal end (50) forms a fluid path between the proximal anddistal medicine chambers (40, 42). The transfer pipe (46) includes aplurality of proximal openings (270) and a middle opening (266). Thetransfer pipe (46) is hollow and forms the fluid path between theproximal most proximal opening (270), which is disposed in the proximalmedicine chamber (40) and the middle opening (266), which is disposed inthe distal medicine chamber (42). While the transfer pipe (46) depictedin FIGS. 6M-60 includes four proximal openings (270) and a middleopening (266), other embodiments may have more or fewer proximal andmiddle openings. Increasing the number of proximal and middle openingsincreases the tolerance for positioning of the transfer pipe (46)/needleproximal end (50) relative to the distal stopper member (42) whilemaintaining an open fluid path between the proximal and distal medicinechambers (40, 42).

After the dual chamber safe injection system is in the transferconfiguration as depicted in FIG. 6N, as more force is applied to theplunger manipulation interface (128), the proximal stopper member (32)can move proximally relative to the distal stopper member (36), becauseliquid in the proximal medicine chamber (40) can move to the distalmedicine chamber (42) via the transfer pipe (46). As the liquid in theproximal medicine chamber (40) is transferred to the distal medicinechamber (42), the liquid can mix with the contents of the distalmedicine chamber (42). In the embodiment depicted in FIGS. 6A and 6B,the liquid in the proximal medicine chamber (40) in the transportconfiguration (FIGS. 6A, 6B, and 6M) is a first, liquid component of amedicine. The content of the distal medicine chamber (42) is a secondcomponent of the medicine. Transferring the liquid from the proximalmedicine chamber (40) to the distal medicine chamber (42) mixes thefirst and second components to form a ready to inject medicine.

As shown in FIG. 6O, continued force applied to the plunger manipulationinterface (128) from the transfer configuration completes the transferof liquids from the proximal medicine chamber (40) to the distalmedicine chamber (42) and places the dual chamber safe injection systeminto a mixed configuration. In the mix configuration the first andsecond components are mixed and the medicine is ready to inject into apatient. The mixed medicine is disposed in the distal medicine chamber(42). Distal movement of the proximal stopper member (32) relative tothe distal stopper member (36) has placed the proximal and distalstopper members (32, 36) into contact and reduced the volume of theproximal medicine chamber (40) to substantially zero. Accordingly,continued force applied to the plunger manipulation interface (128)moves the proximal and distal stopper members (32, 36) together andejects the mixed medicine through a distal opening/outflow port at thedistal end of the transfer pipe (46) and out of the distal medicinechamber (42) through the needle and into the patient. The transfer pipe(46) also contains a lumen plug (268) disposed between the proximal endand the distal end of the interior lumen. The lumen plug (268) blocksthe mixed medicine from being forced retrograde through the flowchannels during injection of the mixed medicine into the patient.

Referring to FIGS. 7A-7L, various aspects of configurations designed tofacilitate injection of multi-part medications and retractions of aneedle into a syringe body are illustrated, wherein two or moremedication components are combined to form an injection combination orsolution shortly before delivery into the patient. In one variation, aliquid first medicine component/diluent (252) may be combined with asubstantially non-liquid second medicine component (254), such as apowdered form, of a drug agent, such as a freeze-dried or lyophilizeddrug component, shortly before injection. The configurations describedherein in reference to FIGS. 7A-7L relate to dual-chamberconfigurations, wherein two or more chambers within the same syringebody (34) are utilized to carry, mix, and inject an injection solution.

Referring to FIGS. 7A and 7B, proximal and distal medicine chambers (40,42) are formed by a distal stopper member (36) in between two portionsof the interior of a syringe body (34), such that the distal medicinechamber (42) contains an air or gas gap, as well as a non-liquidmedication (254); a proximal medicine chamber (40), on the opposite sideof the distal stopper member (36) contains a liquid diluent (252), whichis proximally contained by a proximal stopper member (32). The liquiddiluent (252) is a first component of a medicine and the non-liquidmedication (254) is a second component of the medicine.

Referring to FIG. 7C, and the associated cross sectional view in FIG.7D, various components of a needle coupling assembly (here a so-called“staked” needle coupling assembly (606) is illustrated, but other needleassemblies as described below, including Luer-coupled as well as stakedconfigurations, may be utilized). Lug features (258) are configured toassist with coupling the needle coupling assembly (606) to a needlecover member (63), as shown in FIG. 7A, for example. A small O-ring maybe utilized as a sealing member (260) around the needle shaft, while alarger O-ring may be utilized as a sealing member (262) at the syringebody (34)/needle coupling assembly (606) interface. Alternatively, thesmall O-ring (260) and the large O-ring (262) may be combined into asingle seal that performs both of the O-ring sealing functions. Also,the small O-ring (260) may be used to seal both around the needle shaftand to the syringe body (34).

The needle includes a plurality (e.g., four) of proximal openings/ports(270) configured to allow for entry of a liquid diluent, to be expelledout of a more distally-located middle opening/aperture (266); a lumenplug (268) occludes the needle lumen to create the flow path from theproximal openings (270) to the middle opening (266) under conditionssuch as those described above in reference to FIGS. 6N and 7H. Theneedle also includes a distal opening (264) on the opposite side of thelumen plug (268) from the middle opening (266). The distal opening (264)is fluidly coupled to the needle distal end (48) through the needle toinject liquid into a patient.

Referring to FIG. 7E, a proximal harpoon interface (84) is configured toserially penetrate proximal and distal stopper members (32, 36), andcouple with a coupling feature (such as a needle retention feature areillustrated, for example, in FIGS. 7N and 7P, element 712) in theplunger rod. FIG. 7F illustrates a spike style harpoon couplinginterface (85) that is configured to serially pierce both proximal anddistal stopper members (32, 36) and couple with a coupling feature inthe plunger rod to retract the needle member at least partially into theplunger rod after the injection has been given to the patient.

FIGS. 7A, 7B, and 7G-7P illustrate a sequence of actions for aninjection procedure utilizing a dual chamber safe injection system suchas that described above. Referring to FIGS. 7A and 7B, an injectionassembly is in a stable configuration wherein it may be shipped orbrought to an injection patient care scenario; a first drugcomponent/liquid diluent (252) is isolated from a second non-liquid drugcomponent (254), both within a syringe body on opposite sides of adistal stopper member (36).

FIGS. 7G and 7H illustrate initial insertion movement of the plungerassembly (44), advancing the distal (36) and proximal (32) stoppermembers together relative to the syringe body (34). Referring to FIG.7H, with advancement sufficient to stab the proximal end (50) of theneedle assembly across the distal stopper member (36), a fluid pathwayis formed between the two previously isolated chambers (40, 42) of thesyringe body (34), such that the liquid first drug component (252) inthe proximal medicine chamber (40) may flow into at least one of theproximal openings (270), through the transfer pipe (46), and exit themore distal middle opening (266), to reach the non-liquid second drugcomponent (254) in the distal medicine chamber (42).

FIGS. 71 and 7J illustrate that with further insertion until the stoppermembers (36, 32) are immediately adjacent each other, the liquid firstdrug component/diluent (252) has moved into the distal medicine chamber(42) to join the non-liquid second drug component (254). FIGS. 7K and 7Lillustrate that with time and/or manual agitation, the liquid first drugcomponent/diluent (252) and previously non-liquid second drug component(254) become mixed to form a mixed medication solution (272).

In some embodiment, especially with lyophilized non-liquid second drugcomponents, the mixed medication solution (272) may be formed withminimal or no agitation or time passage. In another embodiment,especially with drugs which are held in suspension or emulsified drugs,vigorous shaking may be necessary to facilitate mixing. In the case ofvigorous shaking it is useful to the user to be able to remove theirthumb from the plunger manipulation interface (128). During transfer ofliquid first medicine component (252) from the proximal to the distalmedicine chambers (40, 42) pressure may build up in the distal medicinechamber (42). This pressure acts upon the proximal and distal stoppermembers (32, 36) to resist stopper motion. The pressure buildup may alsomove the stopper members (32, 36) and plunger manipulation interface(128) proximally if the user does not have their thumb restraining theplunger assembly (44). Mixed configuration latches or “mix clicks” inthe plunger assembly (44) (depicted in FIGS. 9A and 9B and describedbelow) may be utilized to provide resistance to plunger manipulationinterface (128) motion due to pressure buildup and allow the user torelease their thumb from the plunger manipulation interface (128) forshaking or mixing of the drug. The mix clicks may also provide anaudible and/or tactile indication that the transfer of liquid firstmedicine component (252) has been completed. The distal medicine chamber(42) may also include an agitation device, which assists in mixing ofthe medicine components.

With the assembly ready for injection of the mixed solution (272), theneedle cover member (63) may be removed and the patient may be injectedwith the exposed needle distal end (48) with depression/insertion of theplunger assembly (44) and associated stopper members (36, 32) as shownin FIGS. 7M and 7N. Referring to FIGS. 7O and 7P, with fulldepression/insertion of the plunger assembly (44) and associated stoppermembers (32, 36), the sharp needle distal end/point (48) mayautomatically retract at least partially through the distal and proximalstopper members (36, 32) to a safe position within either the syringebody (34), the needle coupling assembly (606), or at least partiallywithin the plunger assembly (44). Automatic retraction of the needle atleast partially within the plunger is described in U.S. patentapplication Ser. Nos. 14/696,342 and 62/416,102, which were previouslyincorporated by reference herein.

Existing lyophilization manufacturing processes perform thelyophilization (freeze-drying) of the solution (e.g., a liquid drug)inside of the syringe chamber which is sealed proximal to the drug witha stopper. The distal tip of the syringe is left open duringlyophilization, exposing the drug to the lyophilization process throughthe inside diameter (“ID”) of the tip of the syringe. This existingprocess generally does not allow for the use of traditional glued-instaked needles, as the needle would have to be in place prior tolyophilization due to the glue curing process. The ID of the traditional25 gauge to 34 gauge staked needles are around to 0.003″. This range ofID is generally too small to allow lyophilization of the drug in areasonable amount of time. The staked needle assembly shown in FIGS.6A-7P uses a Luer taper tip syringe with a tip ID of about 0.040″ thatallows for lyophilization. The staked needle of FIGS. 6A-7P is attachedto the syringe via a snap-fit after lyophilization has taken place,sealing the drug container, and allowing for the use of existinglyophilization manufacturing processes.

While the embodiments depicted in FIGS. 6A-7P transfer liquid through atransfer pipe (46), in other dual chamber embodiments, liquid may betransferred through a bypass channel/passageway formed into a syringebody. The bypass channel may be formed in or adjacent to the wall of aglass syringe using a mandrel during syringe formation. The bypasschannel may have openings into the syringe body that may be selectivelyoccluded by the proximal and distal stopper members to control liquidtransfer. Such embodiments are described in further detail in U.S.patent application Ser. No. 14/696,342, which was previouslyincorporated by reference herein.

A. Exemplary Harpoon Coupling Interfaces

FIGS. 8A and 8B depict two embodiments of dual chamber safe syringesystems having different harpoon coupling interface (87, 88). Theembodiment depicted in FIG. 8A has an articulated needle harpooncoupling interface (87). The embodiment depicted in FIG. 8B has atree-shaped harpoon coupling interface (88). The spring has been omittedfrom FIG. 8B for clarity. These coupling interfaces (87, 88), theircorresponding needle retention features (712), and their use toselectively retract a needle are described in in U.S. patent applicationSer. No. 62/416,102, which was previously incorporated by referenceherein. The different harpoon coupling interfaces (87, 88) can be usedwith the depicted in FIGS. 6A-7P.

B. Mixed Configuration Latch

FIGS. 9A and 9B depict a mixed configuration latch (300) on a plungerassembly (44) usable with the embodiments depicted in FIGS. 6A-8B. Themixed configuration latch (300) tapers distally and is biased (e.g., bya spring) to extend radially from the plunger assembly (44). The mixedconfiguration latch (300) is configured such that, when the dual chambersafe syringe system is in the mixed configuration (i.e., wherein theproximal and distal stopper members are in contact with each other) themixed configuration latch (300) moves distally beyond a detent (302) onthe small diameter flange (33) coupled to the syringe body (34), asshown in FIG. 9B. At that point, the mixed configuration latch (300)extend radially from the plunger assembly (44), preventing proximalmovement of the plunger assembly (44) relative to the syringe body (34).

Preventing proximal movement of the plunger assembly (44) allows a userto release pressure on the plunger manipulation interface (128) withoutallowing the plunger assembly (44) to be driven proximally by thepressure built up in the distal medicine chamber (42) as the liquidfirst medicine component is forced from the proximal medicine chamber(40) into the distal medicine chamber (42).

Radial extension of the mixed configuration latch (300) after radialcompression by the tapered portion passing the detent (302) generates anaudible or tactile signal (i.e., click). The audible or tactile signalindicates to a user that the dual chamber safe syringe system is in themixed configuration, and that the user may release pressure on theplunger manipulation interface (128). The user may also agitate and/orinvert the dual chamber safe syringe system to mix the medicinecomponents (252, 254) after hearing or feeling the audible or tactilesignal.

C. Mixed Configuration Indicator

FIGS. 10A and 10B depict a portion of the dual chamber safe injectionsystems depicted in FIGS. 6A-9B including proximal and distal stoppermembers (32, 36) with a system in transport configuration (FIG. 10A) andmixed configuration (FIG. 10B). Comparing FIGS. 10A and 10B shows thatthe proximal medicine chamber (40) in a system in the transportconfiguration is collapsed when the system is moved to the mixedconfiguration. As described above, the liquid first medicine component(252) in the proximal medicine chamber (40) in a system in the transportconfiguration is transferred to the distal medicine chamber (42) throughat least one proximal opening (270), the transfer pipe (46) and themiddle opening (266).

For optimal performance, the pressure applied to the plungermanipulation interface (128) by a user to move the proximal stoppermember (32) distally relative to the distal stopper member (36) shouldnot exceed the pressure required to transfer liquid through the transferpipe (46) at a maximal rate (“max transfer pressure”). The max transferpressure is determined by various system parameters, including but notlimited to, transfer tube cross-sectional area and length and liquidviscosity. If the applied pressure exceeds the max transfer pressure,the remaining incompressible liquid in the proximal medicine chamber(40) will transfer the applied pressure to the distal stopper member(36), moving the distal stopper member (36) distally relative to thesyringe body (34) and the needle spine assembly (76) coupled thereto.

Moving the distal stopper member (36) relative to the needle spineassembly (76) before reaching the mixed configuration can prematurelyhalt liquid transfer by moving distal stopper member (36) over themiddle opening (266) before all of the liquid in the proximal medicinechamber (40) is transferred to the distal medicine chamber (42). Becausethe lumen plug (268) prevents liquid from traveling from the proximaland middle openings (270, 266) to the distal opening (264), closing themiddle opening (266) with the distal stopper member (36) effectivelystops liquid transfer before completion. With even more appliedpressure, the distal stopper member (36) may move even more distally,placing the middle opening (266) in the proximal medicine chamber (40)before liquid transfer is complete. This also stops liquid transferbefore completion. Accordingly, applying more pressure than the maxtransfer pressure will result in incomplete liquid transfer, which willaffect the dissolving of the substantially non-liquid second medicinecomponent (254), and/or the concentration of the mixed medicationsolution (272).

In order to address the problem of the user applying more pressure thanthe max transfer pressure, the embodiment depicted in FIGS. 10A and 10Bincludes a mixed configuration indicator (304), which is a visualindicator disposed on the syringe body (34). The mixed configurationindicator (304) in FIGS. 10A and 10B is a ring disposed (e.g., painted,etched, etc.) on the syringe body (34) that indicate the approximateoptimal location of the distal edge of the distal stopper member (36)when the system is in the mixed configuration. This visual indicator/cueallows a user to visually detect when the distal stopper member (36) ismoving too far distally relative to the syringe body (34) before thesystem reaches its mixed configuration. When the user detects suchmovement, the user can reduce the pressure applied to the plungermanipulation interface (128) to stop/slow the distal movement of thedistal stopper member (36). In some embodiments, an audible or tactilesignal from the mixed configuration latch (300) indicates to the userwhen the system has reached the mixed configuration and it is safe topush the distal stopper member (36) distally past the mixedconfiguration indicator (304).

Dual chamber safe injection systems with mixed configuration indicators(304) may include directions for use that instruct a user to “not allowthe front/distal stopper to pass the mixed line until you hear a click.”The mixed configuration indicator (304) allows the user to vary appliedpressure to allow the system to transfer liquid with minimal movement ofthe distal stopper member (36). The mixed configuration indicator (304)can eliminate the need for various friction increasing featurespreviously used to control stopper movement during the liquid transferphase of the mixing process.

D. Distal Stopper Bushing and Proximal Stopper Screw

FIGS. 11A-11E illustrate the dual chamber safe injection systemsdepicted in FIGS. 6A-10B in increasing detail to demonstrate variousfeatures of the systems. As best shown in FIG. 11E, while the proximaland distal stopper members (32, 36) start as conventional, off-the-shelfstoppers for injection systems, each of the proximal and distal stoppermembers (32, 36) are modified with additional components to optimize theperformance of the dual chamber safe injection system.

FIG. 11E shows that the distal stopper member (36) is disposed in thesyringe body (34) in an orientation that is the opposite of the typicalorientation for a stopper. In this reverse orientation, the lubriciouscoating (308) on the distal stopper member (36) is facing the proximalmedicine chamber (40), and the female threads on an inner surface of thedistal stopper member (36) are facing the distal medicine chamber (42).On the other hand, the proximal stopper member (32) is disposed in thesyringe body (34) in the typical orientation, such that its lubriciouscoating (306) is facing the proximal medicine chamber (40), and itsfemale threads are facing the plunger assembly (44). The respectivefemale threads of the proximal and distal stopper members (32, 36) areconfigured for attachment. Typically the female threads are used toattach a plunger assembly. However, the dual chamber safe injectionsystems described herein take advantage of the female threads to attachadditional components to optimize performance. The lubricious coatings(306, 308) may be PTFE, which acts as a fluid barrier to protect the(e.g., butyl-rubber) proximal and distal stopper members (32, 36) fromthe first medicine component in the proximal medicine chamber and (40)or vice versa.

A distal stopper bushing (310) is secured to the distal stopper member(36) using an interaction between male threads (312) on the distalstopper bushing (310) and the distally facing female threads on thedistal stopper member (36). The distal stopper bushing (310) is shown inisolation in FIGS. 12A-12D. As shown in FIGS. 11E and 12D, the distalstopper bushing (310) defines an alignment funnel (314) that is distallyfacing when the distal stopper bushing (310) installed in the distalstopper member (36) that is in turn installed in the dual chamber safeinjection system. The distally facing alignment funnel (314) isconfigured to guide a needle proximal end (50) into position whenassembling the dual chamber safe injection system. As also shown inFIGS. 11E and 12D, the distal stopper bushing (310) also defines areceiving space (316) configure to receive the needle proximal end (50)when the dual chamber safe injection system is assembled in thetransport configuration. The receiving space (316) is located adjacentto a “pierce through” section of the rubber distal stopper bushing (310)which is configured to be pierced by the needle proximal end (50) toexpose at least one proximal opening (270) into the proximal medicinechamber (40) to allow liquid transfer. During assembly, the distallyfacing alignment funnel (314) guides the needle proximal end (50) intothe receiving space (316), which secures the needle proximal end (50)during transportation and storage of the dual chamber safe injectionsystem. The alignment funnel (314) also guides the needle proximal end(50) during liquid transfer and/or needle retraction to ensure that theneedle proximal end (50) enters a plunger rod funnel for needleretraction (as described in U.S. patent application Ser. No. 62/416,102,which was previously incorporated by reference herein). The distalstopper bushing (310) also defines a bushing flange (318), which sealsagainst a distally facing surface of the distal stopper member (36) tolimit contact between the second medicine component in the distalmedicine chamber (42) and the distal stopper member (36) duringtransportation and storage of the dual chamber safe injection system.The bushing flange (318) also prevents liquid from leaking between thedistal stopper bushing (310) and the distal stopper member (36) underpressure. In an alternative embodiment, the distal stopper bushing (310)and distal stopper member (36) are integrated into one solid rubberstopper member with the “pierce through” section and the funnel geometrymolded in. A lubricious coating may be applied to the distal, proximaland/or circumferential sides of the distal stopper member (36) and/orthe alignment funnel (314).

FIGS. 12E and 12F depict a guide disc (320) according to anotherembodiment with similar features to the distal stopper bushing (310)described above. The guide disc (320) also defines an alignment funnel(314′) that papers proximally down to a receiving space (316′). Theguide disc (320) also defines radial spring arms (321) which interfacewith the inner surface of the syringe body (34) to center the guide disc(320) and guide the needle proximal end (50) during piercing through thedistal stopper member (36) and into the plunger rod assembly (44) forneedle unlatching and/or retraction (as described in U.S. patentapplication Ser. No. 62/416,102, which was previously incorporated byreference herein). As shown in FIG. 12E, the guide disc (320) can beused with distal stopper members (36′) that are installed in theconventional manner (i.e., facing distally).

A proximal stopper screw (322) is secured to the proximal stopper member(32) using an interaction between male threads (324) on the proximalstopper screw (322) and the proximally facing female threads on theproximal stopper member (32). The proximal stopper screw (322) is shownin isolation in FIGS. 13A-13C. As shown in FIGS. 11E and 13C, theproximal stopper screw (322) defines an alignment funnel (326) and asealing space (328). The sealing space (328) has a length greater thanor equal to the distance between the most proximal opening (270) and themiddle opening (266) (see FIGS. 6N and 60 ).

After the needle proximal end (50) has pierced both the distal andproximal stopper members (36, 32), the alignment funnel (326) isconfigured to guide the needle proximal end (50) into the sealing space(328). During the early injection phase, the middle opening (266)remains in the distal medicine chamber (42), providing a fluid paththrough the transfer pipe (46) into the plunger assembly (44). Thesealing space (328) of the proximal stopper screw (322) is configured toprevent liquid (e.g., mixed medication solution (272)) from travelingretrograde in the middle opening (266) through the transfer pipe (46)and out the proximal openings (270). The proximal stopper screw (322)has a proximal septum (330) that maintains the seal preventingretrograde liquid travel until the middle opening (266) is disposed inthe proximal stopper screw (322) and sealed thereby. The proximalstopper screw (322) may be made with a rigid plastic portion (includingthe male threads (324)) and a rubber or elastomer portion defining thealignment funnel (326) and the sealing space (328), and including theproximal septum (330).

Exemplary Dual Chamber Safe Cartridge Systems

FIGS. 14A and 14B respectively depict similar sized cartridge (134) andsyringe body (34). Both the cartridge (134) and the syringe body (34)may be made from glass. While the syringe body (34) is configured foruse in an injection system, the cartridge (134) is configured forstorage of substances (e.g., medications). This results in severaldifferences between cartridges (134) and syringe bodies (34). Forinstance, while the proximal end of the syringe body (34) includes aconventional integral syringe flange (38), the proximal end of thecartridge (134) does not include an integral flange. Further, while thedistal end of the syringe body (34) includes a Luer taper configured toallow snapping engagement of a needle coupling assembly (606), thedistal end of the cartridge (134) includes a flange (102) configured forsecuring a conventional cartridge seal (not shown). Conventionalcartridge seals include an elastically compressible sealing member atleast partially surrounded by an elastically deformable closure (e.g.,an aluminum ring). As shown in FIGS. 14A and 14B, the distal opening ofthe cartridge (134) is significantly larger than the correspondingdistal opening of the syringe body (34). This provides more airflow forlyophilization as described above.

FIGS. 14C and 14D depict a dual chamber safe injection system builtaround a cartridge (134) instead of a syringe body (34). Thesubstitution of a cartridge (134) for a syringe body (34) results in twochanges to the dual chamber safe injection system. The first is that thesmall diameter flange (33) is glued or press fit onto the cartridge(134) instead of being coupled to a syringe flange.

The second difference for dual chamber safe injection systems builtaround a cartridge (134) involves connection of the needle couplingassembly (606) to the distal end of the cartridge (134) as shown inFIGS. 14C-16H. As shown in FIG. 14E, the needle coupling assembly (606)is coupled to the distal end of the cartridge (134) using a collet (104)and a sleeve (106). The collet (104) may be welded onto a base plate ofthe needle coupling assembly (606). FIGS. 15A and 15B show a systemassembly step in which a needle distal portion (50) of a needle couplingassembly (606) is inserted into a distal medicine chamber (42). As shownin FIGS. 15B and 15D, the collet (104) is expandable to partially passproximally over the flange (102) on the distal end of the cartridge(134). As shown in FIGS. 15D and 15E after a proximal end (108) of thecollet (104) has passed proximally of the flange (102), the sleeve (106)can be slid proximally over the collet (104) to prevent the collet (104)from opening and releasing from the flange (102). Securing the sleeve(106) over the collet (104) on the flange (102) secures the needlecoupling assembly (606) to the distal end of the cartridge (134).

FIGS. 16A-16C again show the attachment of the coupling assembly (606)to the distal end of the cartridge (134). FIGS. 16A and 16B also depictthe needle proximal end (50), showing the alignment funnel (314) on thedistal stopper bushing (310) guiding the needle proximal and (50) intothe receiving space (316) during assembly of the dual chamber safeinjection system. FIG. 16D shows the attachment of the small diameterflange (33) to the proximal end of the cartridge (134), and insertion ofthe plunger assembly (44) and the proximal stopper member (32) securesthereto into the cartridge (134). The dual chamber safe injection systemwith the cartridge (134) depicted in FIG. 16D is ready to transport,store, and use (i.e., mixing, injecting and automatic retraction)following steps exactly identical to those depicted for the dual chambersafe injection system with the syringe in FIGS. 7A-7P.

FIGS. 16G and 16H depict in detail the interface between the collet(104) and the flange (102) both without (FIG. 16G) and with (FIG. 16H)the sleeve (106). FIGS. 16G and 16H also depict a needle seal (110)disposed in the needle coupling assembly (606) and configured to fluidlyseal the annular space between the inner diameter of the opening in thedistal end of the cartridge (134) and the outer diameter of the needlespine assembly (76). The needle seal (110) may be made from anelastically deformable material such as rubber. The needle seal (110)also includes a pair of glands (112) that extend into an inner diameterof the needle seal (110). The glands (112) function like two O-ringsthat seal against the needle spine assembly (76).

Various features of the dual chamber safe injection system built arounda cartridge (134) can also be used with auto injectors or pen injectors.The cartridges of these systems may also incorporate an integral glassor plastic finger flange similar to what is employed on the syringebased systems.

Exemplary Dual Chamber Safe Injection Systems with Luer Connectors

FIGS. 17A-19D depict various dual chamber safe injection systems withLuer connectors (114) at their distal ends. For use with a cartridge(134), as shown in FIGS. 17A-17H, a female Luer lock connector (114)with internal threads is attached to a collet (104) and a sleeve (106)like the ones depicted in FIGS. 14A-16H and described above to form aneedle hub (116). The collet (104) and the sleeve (106) can be used toattach the needle hub (116) to the distal end of the cartridge (134) asdescribed above for attaching the needle coupling assembly (606) to thecartridge (134) depicted in FIGS. 14A-16H. The distal end of the femaleLuer lock connector (114) is temporarily sealed with a removable Luercap (118). Once the needle hub (116) is attached to the cartridge (134),the Luer cap (118) can be removed and a Luer needle (120) may beattached to the needle hub (116) and the dual chamber safe injectionsystem using the female Luer lock connector (114) as shown in FIG. 17E.

After the Luer needle (120) is attached to the needle hub (116) and thedual chamber safe injection system, the system with is ready totransport, store, and use (i.e., mixing, injecting and automaticretraction) following steps exactly identical to those depicted for thedual chamber safe injection system with the syringe in FIGS. 7A-7P.Mixing, injection and retraction steps similar to those depicted inFIGS. 7A-7P are depicted for a dual chamber safe injection system with afemale Luer lock connector (114) in FIGS. 17A-17H.

Using a female Luer lock connector (114) and a replaceable Luer needle(120) leads to one additional complication. A proximal end (122) of theLuer needle (120) must be connected to a transfer pipe (46) whileconnecting the Luer needle (120) to the female Luer lock connector (114)on the needle hub (116). During attachment of the Luer needle (120), aneedle cover member (63) is configured to guide the Luer needle (120)into the needle hub (116), thereby aligning the proximal end (122) ofthe Luer needle (120) with the transfer pipe (46) to improve connectionbetween the Luer needle (120) and the transfer pipe (46). Guiding needlecover members are described in U.S. patent application Ser. No.14/696,342, which was previously incorporated by reference herein. FIGS.17J-17K and 18C-18F show the connection between the Luer needle (120)and the transfer pipe (46). As seen in these figures, the male Luer lockconnector (124) with external threads on the Luer needle (120) guide theproximal end (122) of the Luer needle (120) into the transfer pipe (46)for a secure connection there between. The threads on the Luer lockconnectors (114, 124) force the proximal end (122) of the Luer needle(120) into the transfer pipe (46) for a hermetic press fit or snap fit.The distal end of the transfer pipe (46) also includes a latch groove(111) configured to interact with one or more cantilevered latch members(616) to prevent the transfer pipe from being forced proximally into thecartridge (134) during attachment of the Luer needle (120), as describedbelow.

FIGS. 19A-19D illustrate an embodiment wherein a dual chamber safeinjection system with a female Luer lock connector (114) at its distalend is used for mixture (with or without a Luer cap (118) on) andinjection without a Luer needle. The connector (114) may also be a Luertaper or Luer slip, or other fluid connector. As shown in FIG. 19D, thedual chamber safe injection system can be connected to any Luer lockaccess port (130) such as that connected to an IV tube and an IV bag. Insuch an embodiment, the dual chamber safe injection system does notretract because the retraction mechanism is not necessary as there is nosharp needle. In this case, the transfer pipe (46) may be stationary toallow for transfer of the liquid from the proximal medicine chamber (40)to the distal medicine chamber (42), and then allow for the injection ofthe mixed medicine (272) into the IV tube or other injection systems.

While the dual chamber safe injection system with Luer connectorembodiments depicted in FIGS. 17A-19D involve cartridges, Luerconnectors can also be used with syringes and other dual chamber safeinjection systems.

Exemplary Safe Injection Systems for Metal Sensitive Medicines

An increasing number of injectables (e.g., medicines) are sensitive todegradation during storage by contact with metals, such as that found ona needle. FIGS. 20A-20D depict use of a prefilled dual chamber safeinjection system to minimize the exposure of such sensitive medicines tometal during storage. For instance, the sensitive medicine (132) can beprefilled in the system and stored in the proximal medicine chamber (40)as shown in FIG. 20A, which depicts a transport configuration for thedual chamber safe injection system. As such the sensitive medicine (132)is only exposed to the glass of the syringe body (34) and thehydrophilic or lubricious coatings (e.g., PTFE) on the proximal anddistal stopper members (32, 36) during transportation and storage. Thedistal medicine chamber (42) contains only the needle proximal end (50)and does not contain any injectable. In effect, the distal stoppermember (36) separates the sensitive medicine (132) from the metal needleproximal end (50) to which it is sensitive.

Directly before injection, a user applies pressure to the plungermanipulation interface (128), thereby pushing the proximal and distalstopper members (32, 36) and the sensitive medicine (132) containedthere between distally. The needle proximal end (50) is configured suchthat it has a single opening located just proximal of the distal stoppermember (36) when the distal stopper member (36) is positioned at adistal end of the syringe body (34), as shown in FIG. 20B. Accordingly,the dual chamber safe injection system is ready to inject as depicted inFIG. 20B. From the configuration depicted in FIG. 20B, further userpressure on the plunger manipulation interface (128) injects thesensitive medicine (132) through the needle distal end (48) andcollapses the proximal medicine chamber (42), as shown in FIG. 20C.Moving from FIG. 20C to FIG. 20D, the needle spine assembly (76) isretracted into the syringe body (34) and at least partially into theplunger assembly (44) as described in U.S. patent application Ser. Nos.14/696,342 and 62/416,102, which were previously incorporated byreference herein. Therefore, time of the exposure of the sensitivemedicine (132) to the metal of the needle spine assembly (76) isminimized to the time it takes to complete an injection.

While the dual chamber safe injection system depicted in FIGS. 20A-20Dis configured for use with the syringe, similar systems can beconfigured for use with a cartridge containing sensitive medicine. Whilethe dual chamber safe injection system depicted in FIGS. 20A-20Dinvolves direct injection from the proximal medicine chamber (40), othersystems may involve movement of the sensitive medicine from the proximalmedicine chamber (40) to the distal medicine chamber (42) beforeinjection, as shown in FIGS. 22A-22D.

Needle Latching Member

FIGS. 21A-21D depict the interaction between the latch groove (111) onthe distal end of the transfer pipe (46) and a needle latching member(612) to prevent proximal movement of the needle spine assembly (76)(including the transfer pipe (46)) before injection is completed.

FIG. 21A shows a transfer pipe (46) with a latch groove (111) formedthereon and a proximal end of a distal needle end (48) inserted therein.In one embodiment, the proximal end of the distal needle end (48) may bethe proximal end of the Luer needle, as described above. The transferpipe (46) has a necked-down or radially-reduced latch groove (111) thatis configured to interface with a latching member (612) and movableblock member (614) such that during system assembly and use (e.g.,mixing and injection), the needle spine assembly (76), including thetransfer pipe (46), remains fixed in position relative to the syringebody (34), but after complete insertion of the plunger assembly relativeto a small diameter flange (33—see, for example, FIG. 7N) (i.e., near orafter full expulsion of the medicine which may be contained within thedistal medicine chamber 42 of the syringe body 34), the needle spineassembly (76) is forced distally by the advancement of the plunger,advancing the movable block member (614) relative to the distal housingportion (610) such that the plurality (two are illustrated) ofcantilevered latch members (616) of the latch member (612) are urged outof the way by the movable block member (614) to allow the needle spineassembly (76) (i.e., the needle distal end (48), transfer pipe (46), andproximal end (50)) to be retracted, thereby placing the needle distalend (48) safely within the plunger assembly (44). Alternatively, theneedle distal end (48) may be retracted to a position below the outersurface of the distal housing portion (610) to safely protect the sharppoint from the user. In other words, the cantilevered latch members(616) retain the position of the needle distal end (48) during injectionand needle/syringe assembly, until they are pushed out of the way by themovable block member (614) at full plunger insertion (see FIG. 21D),after which the needle is free to be withdrawn as U.S. patentapplication Ser. Nos. 14/696,342 and 62/416,102, which were previouslyincorporated by reference herein.

The movable block member (614) includes a smaller distal portion (617)and a larger proximal portion (618) to increase the force needed tounlatch the needle spine assembly (76). The larger proximal portion(618) is configured to create a block outer diameter (622) dimensionthat will interfere with the inner diameter (624) of the latch (612) toincrease the force to slide the movable block, thus increasing the forceto unlatch the needle.

reduces the torque applied to the cantilevered latch members (616),thereby increasing the force needed to unlatch.

Vacuum Assisted Dual Chamber Safe Injection System

FIGS. 23-34 depict various aspects of a vacuum assisted dual chambersafe injection system similar to the ones depicted in FIGS. 6A-10B. Thedual chamber safe injection system has a conventional off-the-shelfpre-filled syringe body (34) with proximal and distal stopper members(32, 36) disposed therein. The proximal and distal stopper members (32,36) together with the syringe body (34) define proximal and distalmedicine chambers (40, 42). The proximal and distal stopper members (32,36) occlude the proximal and distal ends of the proximal medicinechamber (40). The distal stopper member (36) occludes a proximal end ofthe distal medicine chamber (42). The dual chamber safe injection systemcontrols transfer of a first medicine component from the proximalmedicine chamber (40) to the distal medicine chamber (42) and exit of amixed/combined medicine from the distal medicine chamber (42) distallysubject to sequential insertion of a plunger assembly relative to thesyringe body (34) to various degrees by a user. The plunger assemblyincludes the proximal stopper member (32), a plunger housing member (69)and a plunger manipulation interface (128). The first medicine componentlocated in the proximal medicine chamber (40) may be a liquid such asaqueous or oil based medicine solutions, a gel, or the first medicinecomponent may be a diluent for mixing with the second medicine componentin the distal medicine chamber (42). The second medicine component inthe distal medicine chamber (42) may be a dry form medicine such as apowder, microspheres, emulsion, lyophilized or freeze dried medicine, ora cake like solid medicine. The second medicine component in the distalmedicine chamber (42) may also be a liquid that mixes with the firstmedicine component from the proximal medicine chamber (40).

As described above, the dual chamber safe injection system proximal anddistal stopper members (32, 36) are configured to be pierced by proximalneedle end (50) at an appropriate time to assist with medicationtransfer. FIG. 23 illustrates a pre-utilization assembly with a needlecover (63) in place to mechanically isolate the distal needle end (48).The needle cover (63) may be removed and the assembly readied forinjection into a patient. In some embodiments (not shown), the needlecover member (63) includes a vent (not shown) for allowing pressureresulting from the transfer and mixing of the medicine components toescape from inside the syringe body (34) while preventing contaminationfrom entering the syringe body (34). However, such vented needle covermembers are not always desirable.

Without venting, pressure builds in the distal medicine chamber (42) asthe first medicine component is transferred under pressure from theproximal medicine chamber (40) to the distal medicine chamber (42).Pressure build up in the distal medicine chamber (42) may cause liquid(e.g., the mixed medicine) to be expelled from the distal medicinechamber (42) (e.g., through the needle distal end (48) before injection.

Accordingly, the vacuum assisted dual chamber safe injection systemdepicted in FIG. 23 includes a partial vacuum (e.g., 0.1 ATM or 90%vacuum) in the distal medicine chamber (42) before transfer of liquidfrom the proximal medicine chamber (40). The partial vacuum assiststransfer of liquid from the proximal medicine chamber (40). Forinstance, after a portion of the transfer pipe (46) is pushed throughthe proximal stopper member (32) such that a proximal opening (270, seeFIG. 29 ) is disposed in the proximal medicine chamber (40), the partialvacuum in the distal medicine chamber (42) draws liquid from theproximal medicine chamber (40) into the distal medicine chamber (42).The partial vacuum reduces the amount of distally directed force thatmust be applied to the proximal stopper member (32) via the plungerassembly to transfer the liquid from the proximal medicine chamber (40)into the distal medicine chamber (42). Transferring the liquid also atleast partially releases the vacuum in the distal medicine chamber (42).

As shown in FIG. 24 , the partial vacuum in the distal medicine chamber(42) produces a force (“Fv”) on the distal stopper member (36), whichmust be temporarily resisted to maintain the dual chamber safe injectionsystem in its transport/storage/pre-mixing configuration. The distallydirected force (Fv) on the distal stopper member (36) is approximatelythe difference between the pressure in the proximal medicine chamber(40) and the pressure in the distal medicine chamber (42) multiplied bythe area of the distal stopper member (36). In one embodiment:

-   -   pressure in the proximal medicine chamber (40)=1 ATM=14.7 psi    -   pressure in the distal medicine chamber (42)=0.1 ATM=0.15 psi    -   area of distal face of standard 3cc stopper=0.09 int    -   force (Fv) on distal stopper member (36)=0.09 (14.7-0.15)=1.31        lbs        The resistance of the distal stopper member (36) to puncture by        the harpoon coupling interface (not shown) may be sufficient to        overcome the 1.31 lbs of force (Fv). However, with a sharper        harpoon coupling interface or a less puncture resistant distal        stopper member (36), the partial vacuum in the distal medicine        chamber (42) may result in premature puncture of the distal        stopper ember (36) by the harpoon coupling interface and even        premature transfer of liquid from the proximal medicine chamber        (40) into the distal medicine chamber (42).

FIGS. 25 and 26 depict a distal stopper bushing (310) which includes aproximal gate (332). The distal stopper bushing (310) is configured tobe screwed into the distal end of the distal stopper member (36). Theproximal gate (332) includes a pair of movable arms (334), which arebiased toward each other by respective spring elements (336). As such,the proximal gate (332) has two configurations: a closed configuration,in which the harpoon coupling interface cannot pass through the proximalgate (332); and an open configuration, in which the harpoon couplinginterface can pass through the proximal gate (332). In the openconfiguration, the movable arms (334) are forced apart from each other(e.g., by relative movement of the harpoon coupling interface and thedistal stopper member (36) to open the gate (332), as shown below).

When the dual chamber injection system is in thetransport/storage/pre-mixing configuration (see FIGS. 23, 24, 27, and 28) the gate (332) is in the closed configuration. The closed gatetransfers the force (Fv) generated by the partial vacuum in the distalmedicine chamber (42) to the harpoon coupling interface and the needlespine assembly (76) without piercing the distal stopper member (36),because the closed gate (322) prevents the harpoon coupling interfacefrom contacting the distal stopper member (36), as shown in FIGS. 27 and28 . The harpoon coupling interface (89, see FIG. 28 ) includes aproximal shoulder (90) that interferes with the closed gate (322) toprevent the harpoon coupling interface (89) from passing therethrough.The harpoon coupling interface (89) has a hollow 3D arrowhead shape asdescribed in U.S. Utility patent application filed on Nov. 1, 2017 underattorney docket number CM.20015.00 and, entitled “SYSTEM AND METHOD FORSAFETY SYRINGE,” the disclosure of which has been previouslyincorporated by reference herein.

After a sufficient amount of distally directed force has been applied toplunger assembly, the distally directed force applied to the plunger,with the force (Fv) on distal stopper member (36) from the partialvacuum in the distal medicine chamber (42), overcomes the bias of thespring elements (336) in the arms (334) of the gate (332) to move thegate (332) from the closed configuration to the open configuration. Thenthe harpoon coupling interface (89) pierces the distal stopper member(36) partially followed by the transfer pipe (46), as shown in FIG. 29 .Because the transfer pipe (46) has a smaller outer diameter than thedistal end of the harpoon coupling interface (89), the gate (332) closesafter proximal end of the harpoon coupling interface (89) passtherethrough.

Movement of the needle spine assembly (76) through the distal stoppermember (36) is then temporarily halted by a distal shoulder (92) formedon the needle joining member (83) on the needle spine assembly (76),which has a larger outer diameter than the transfer pipe (46). Thedistal shoulder (92) will not pass through the closed gate (322),thereby holding the needle spine assembly (76) and the distal stoppermember (36) in the position depicted in FIG. 29 . In this position, thetransfer pipe (46) spans the distal stopper member (36) and allowstransfer of liquid therethrough. The partial vacuum in the distalmedicine chamber (42) and the distally directed force has been appliedto plunger assembly pull and push the liquid from the proximal medicinechamber (40) to the distal medicine chamber (42). Mechanicalinterference between the distal shoulder (92) and the closed gate (322)minimizes movement of the distal stopper member (36) during liquidtransfer.

FIG. 30 depicts a configuration of the dual chamber safe injectionsystem after liquid transfer from the proximal medicine chamber (40) tothe distal medicine chamber (42) is substantially complete. The proximalstopper member (32) seals opening in the harpoon coupling interface (89,see FIG. 29 ) and the transfer pipe (46, see FIG. 29 ), stopping theliquid transfer. The partial vacuum in the distal medicine chamber (42)provides a space in the distal medicine chamber (42) after liquidtransfer to allow the user to mix first and second medicine componentsby agitating the components.

FIG. 31 depicts a configuration of the dual chamber safe injectionsystem after sufficient distally directed force has been applied toplunger assembly to overcome the mechanical interference between thedistal shoulder (92, see FIG. 29 ) and the closed gate (322, see FIG. 29) (i.e., by opening the gate (322)). After the distal and proximalstopper members (36, 32) are no longer prevented from moving distally bythe distal shoulder (92, see FIG. 29 ) and the closed gate (322, seeFIG. 29 ), the partial vacuum collapses the space by moving the distaland proximal stopper members (36, 32) distally. Distally directed forceapplied to plunger assembly may also assist in collapsing the space inthe distal medicine chamber (42) (compare FIGS. 30 and 31 ).

After the partial vacuum collapses the space in the distal medicinechamber (42), the distal medicine chamber may include a small air bubblethat does not need to be purged before injection. Accordingly, vacuumassisted dual chamber safe injection systems can function withoutpurging unlike other injection systems. Consequently, the vacuumassisted dual chamber safe injection systems described herein can beused with auto injectors, pens, and other “reusable” or “disposable”housing interfaces without purging.

FIG. 32 depicts a configuration of the dual chamber safe injectionsystem after the needle-latching member (612) has been disengaged fromthe needle spine assembly (76) and the harpoon coupling interface (89)has been secured to the needle retention feature, as described above.The energy storage member has been omitted from FIG. 32 for clarity.

FIG. 33 depicts a configuration of the dual chamber safe injectionsystem after a retraction mechanism has been triggered to retract theneedle spine assembly (76) proximally relative to the syringe body (34)until the sharp end of the needle distal end (48) is in a safe positionat least in the needle hub, as described above. The energy storagemember has been omitted from FIG. 33 for clarity.

FIG. 34 depicts a distal stopper bushing (310) which includes a proximalgate (332) according to another embodiment. The difference between thedistal stopper bushing (310) in FIG. 34 and the distal stopper bushing(310) in FIGS. 25-28 is the design of the proximal gate (332). In theproximal gate (332) depicted in FIG. 34 , the pair of movable arms (334)rotate about respective self-energizing hinges (338) when the distalshoulder (92) presses against the movable arms (334) in the proximaldirection. The force of the distal shoulder (92) on the movable arms(334) causes the arms to move closer to each other, thereby securing thetransfer tube (46) to the movable arms (334). This secures the transfertube (46) in an optimal position for liquid transfer. The position ofthe transfer tube (46) in the secured position can be adjusted bymodifying the axial length of the self-energizing hinges (338) to adjustthe force on the transfer tube (46) from the movable arms (334). Afterliquid transfer is complete, increased distally directed force on theplunger assembly overcomes the mechanical interference between thedistal shoulder (92) and the closed gate (322) to allow for injection.

The vacuum assisted dual chamber safe injection system depicted in FIGS.23-33 and described herein facilitate transfer of liquids from theproximal medicine chamber (40) to the distal medicine chamber (42) bypulling liquid into the distal medicine chamber (42) and by minimizingpressure buildup in the distal medicine chamber (42) with liquidtransfer. The vacuum assisted dual chamber safe injection system alsoincludes a distal stopper bushing (310) with a proximal gate (332) toprevent premature movement of the distal stopper member (36) caused bythe partial vacuum in the distal medicine chamber (42).

Various exemplary embodiments of the invention are described herein.Reference is made to these examples in a non-limiting sense. They areprovided to illustrate more broadly applicable aspects of the invention.Various changes may be made to the invention described and equivalentsmay be substituted without departing from the true spirit and scope ofthe invention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processact(s) or step(s) to the objective(s), spirit or scope of the presentinvention. Further, as will be appreciated by those with skill in theart that each of the individual variations described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinventions. All such modifications are intended to be within the scopeof claims associated with this disclosure.

Any of the devices described for carrying out the subject diagnostic orinterventional procedures may be provided in packaged combination foruse in executing such interventions. These supply “kits” may furtherinclude instructions for use and be packaged in sterile trays orcontainers as commonly employed for such purposes.

The invention includes methods that may be performed using the subjectdevices. The methods may comprise the act of providing such a suitabledevice. Such provision may be performed by the end user. In other words,the “providing” act merely requires the end user obtain, access,approach, position, set-up, activate, power-up or otherwise act toprovide the requisite device in the subject method. Methods recitedherein may be carried out in any order of the recited events which islogically possible, as well as in the recited order of events.

Exemplary aspects of the invention, together with details regardingmaterial selection and manufacture have been set forth above. As forother details of the present invention, these may be appreciated inconnection with the above-referenced patents and publications as well asgenerally known or appreciated by those with skill in the art. Forexample, one with skill in the art will appreciate that one or morelubricious coatings (e.g., hydrophilic polymers such aspolyvinylpyrrolidone-based compositions, fluoropolymers such astetrafluoroethylene, PTFE, hydrophilic gel or silicones) may be used inconnection with various portions of the devices, such as relativelylarge interfacial surfaces of movably coupled parts, if desired, forexample, to facilitate low friction manipulation or advancement of suchobjects relative to other portions of the instrumentation or nearbytissue structures. The same may hold true with respect to method-basedaspects of the invention in terms of additional acts as commonly orlogically employed.

In addition, though the invention has been described in reference toseveral examples optionally incorporating various features, theinvention is not to be limited to that which is described or indicatedas contemplated with respect to each variation of the invention. Variouschanges may be made to the invention described and equivalents (whetherrecited herein or not included for the sake of some brevity) may besubstituted without departing from the true spirit and scope of theinvention. In addition, where a range of values is provided, it isunderstood that every intervening value, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention.

Also, it is contemplated that any optional feature of the inventivevariations described may be set forth and claimed independently, or incombination with any one or more of the features described herein.Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin claims associated hereto, the singular forms “a,” “an,” “said,” and“the” include plural referents unless the specifically stated otherwise.In other words, use of the articles allow for “at least one” of thesubject item in the description above as well as claims associated withthis disclosure. It is further noted that such claims may be drafted toexclude any optional element. As such, this statement is intended toserve as antecedent basis for use of such exclusive terminology as“solely,” “only” and the like in connection with the recitation of claimelements, or use of a “negative” limitation.

Without the use of such exclusive terminology, the term “comprising” inclaims associated with this disclosure shall allow for the inclusion ofany additional element—irrespective of whether a given number ofelements are enumerated in such claims, or the addition of a featurecould be regarded as transforming the nature of an element set forth insuch claims. Except as specifically defined herein, all technical andscientific terms used herein are to be given as broad a commonlyunderstood meaning as possible while maintaining claim validity.

The breadth of the present invention is not to be limited to theexamples provided and/or the subject specification, but rather only bythe scope of claim language associated with this disclosure.

1. A system for mixing drug products and injecting, comprising: acylindrical injection body defining a proximal opening and a distalneedle interface at a distal end thereof; proximal and distal stoppermembers disposed in the cylindrical injection body, forming a proximaldrug chamber between the proximal and distal stopper members and adistal drug chamber between the distal stopper member and the distal endof the cylindrical injection body; a plunger member defining a plungerinterior and configured to insert the proximal stopper member relativeto the cylindrical injection body a needle hub assembly coupled to thedistal needle interface of the cylindrical injection body, the needlehub assembly including a needle having a needle proximal end feature, ahub, and a needle latching member configured to couple the needle to thehub, wherein first and second sizes of the respective proximal anddistal drug chambers can be modified by movement of the proximal anddistal stopper members relative to the cylindrical injection body,wherein the distal stopper includes a funnel disposed at a distal endthereof, the funnel tapering in a proximal direction, such that an innerdiameter of a distal end of the funnel is larger than an inner diameterof a proximal end of the funnel, and wherein the distal stopper membercomprises a proximal gate having a closed configuration wherein theneedle proximal end feature cannot pass through the proximal gate, andan open configuration wherein the needle proximal end feature can passthrough the proximal gate.
 2. The system of claim 1, wherein theproximal and distal drug chambers respectively contain first and secondcomponents of a drug to be mixed together prior to injecting into apatient.
 3. The system of claim 1, wherein the system has a transportconfiguration wherein the needle proximal end feature is disposed in thedistal drug chamber, a transfer configuration wherein the needleproximal end feature has at least partially pierced the distal stoppermember and is at least partially disposed in the proximal drug chamber,and a mixed configuration wherein the proximal and distal stoppermembers are in contact with each other, thereby transferring a firstdrug component from the proximal drug chamber to the distal drug chamberto mix the first drug component with a second drug component in thedistal drug chamber.
 4. The system of claim 3, wherein the needlecomprises: a distal end opening; a middle opening disposed in the distaldrug chamber when the system is in the transport, transfer, and mixedconfigurations; and a proximal opening disposed in the proximal drugchamber when the system is in the transfer configuration.
 5. The systemof claim 4, wherein the needle further comprises a plurality of proximalopenings, the proximal opening being one of the plurality of proximalopenings, wherein at least some of the plurality of proximal openingsare disposed in the proximal drug chamber when the system is in thetransfer configuration, and wherein at least some of the plurality ofproximal openings are configured to be occluded by the proximal stoppermember when the system is in the mixed configuration.
 6. The system ofclaim 5, the proximal stopper member comprising a plug configured toocclude at least some of the plurality of proximal openings when thesystem is in the mixed configuration.
 7. The system of claim 6, whereina length of the plug is greater than a distance between a proximal mostopening of the plurality of proximal openings and a distal most openingof the plurality of proximal openings.
 8. The system of claim 3, thecylindrical injection body comprising a position indicator configured tobe adjacent with a distal end of the distal stopper when the system isin the mixed configuration.
 9. The system of claim 3, the plunger membercomprising a retention clip configured to be selectively coupled to thecylindrical injection body when the system is in the mixed configurationto prevent proximal movement of the plunger member relative to thecylindrical injection body.
 10. The system of claim 9, wherein theretention clip is configured to generate an audible signal when theretention clip is selectively coupled to the cylindrical injection body.11. The system of claim 1, wherein the proximal and distal stoppermembers each includes a respective opposing surface, wherein theopposing surface of the proximal stopper member faces a distaldirection, and wherein the opposing surface of the distal stopper memberfaces a proximal direction. and wherein the proximal and distal stopperscomprising respective first and second polymer coatings on respectiveopposing surfaces thereof, such that the proximal drug chamber isdefined by the cylindrical injection body and the first and secondpolymer coatings.
 12. The system of claim 1, wherein the distal drugchamber contains a partial vacuum.
 13. The system of claim 12, whereinthe proximal gate comprises a pair of movable arms operatively coupledto a pair of spring elements, the pair of spring elements biasing theproximal gate in the closed configuration.
 14. The system of claim 12,wherein the needle proximal end feature comprises a proximal shoulderthat cannot past through the proximal gate in the closed configuration,but can pass through the proximal gate in the open configuration. 15.The system of claim 14, wherein the needle comprises a distal shoulderthat cannot past through the proximal gate in the closed configuration,but can pass through the proximal gate in the open configuration, andwherein the distal shoulder is distal of the proximal shoulder.
 16. Thesystem of claim 12, wherein the proximal gate comprises a pair ofmovable arms operatively coupled to a pair of self-energizing hinges.17. The system of claim 1, wherein the funnel is configured to receivethe needle proximal end feature and guide the needle into coaxialalignment with the distal stopper member.
 18. A method for mixing andinjecting medicine into a patient, comprising: providing a systemcomprising a cylindrical injection body defining a proximal opening anda distal needle interface at a distal end thereof, proximal and distalstopper members disposed in the cylindrical injection body, forming aproximal medicine chamber between the proximal and distal stoppermembers and a distal medicine chamber between the distal stopper memberand the distal end of the cylindrical injection body, a plunger memberdefining a plunger interior and configured to insert the proximalstopper member relative to the cylindrical injection body, and a needlemember having a distal needle tip, a medicine passage, a plurality oftransfer openings, and a proximal end; and wherein the distal stopperincludes a funnel disposed at a distal end thereof, the funnel taperingin a proximal direction, such that an inner diameter of a distal end ofthe funnel is larger than an inner diameter of a proximal end of thefunnel; advancing the plunger member to pierce the proximal end of theneedle member through the distal stopper to allow the passage of a firstmedicine component from the proximal medicine chamber through themedicine passage and into the distal medicine chamber to allow mixing ofthe first medicine component with a second medicine component in thedistal medicine chamber to form a mixed medicine; and advancing theplunger member to inject the mixed medicine into a patient, wherein thedistal stopper member comprises a proximal gate having a closedconfiguration wherein the needle proximal end feature cannot passthrough the proximal gate, and an open configuration wherein the needleproximal end feature can pass through the proximal gate.
 19. The methodof claim 18, wherein the system has a transport configuration whereinthe needle proximal end feature is disposed in the distal drug chamber,and wherein advancing the plunger member to pierce the proximal end ofthe needle member through the distal stopper to allow the passage of afirst medicine component from the proximal medicine chamber through themedicine passage and into the distal medicine chamber places the systemin a transfer configuration.
 20. The method of claim 19, furthercomprising advancing the plunger member to position the proximal anddistal stopper members in contact with each other, thereby transferringthe first medicine component from the proximal drug chamber to thedistal drug chamber to mix the first medicine component with the secondmedicine component in the distal drug chamber, to place the system in amixed configuration.